We are attempting to improve methods for measuring circulating proinsulin and C-peptide. The serum concentrations of these peptides will then be determined in patients with diabetes, islet cell tumors and other metabolic and endocrine disorders. Patients with abnormalities in the structure of their circulating insulin and/or proinsulin molecules have been identified. These peptides will now be characterized and we will attempt to elucidate the specific sequence defect which is present. New, simplified methods for characterizing insulin antibodies have been established. The role of the antibodies in modifying diabetic control and in the syndrome of "autoimmune hypoglycemia" will be investigated.